Genes known to escape X chromosome inactivation predict co-morbid chronic musculoskeletal pain and posttraumatic stress symptom development in women following trauma exposure.
Genes known to escape X chromosome inactivation predict co-morbid chronic musculoskeletal pain and posttraumatic stress symptom development in women following trauma exposure.
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已知逃避 X 染色体失活的基因可预测女性在遭受创伤后出现的并发慢性肌肉骨骼疼痛和创伤后应激症状。
DOI：
10.1002/ajmg.b.32706
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Linnstaedt,SarahD
中科院分区：
文献类型：
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作者：
Yu,Shan;Chen,Constance;Pan,Yue;Kurz,MichaelC;Datner,Elizabeth;Hendry,PhyllisL;Velilla,Marc-Anthony;Lewandowski,Christopher;Pearson,Claire;Domeier,Robert;McLean,SamuelA;Linnstaedt,SarahD
共病慢性肌肉骨骼疼痛（CMSP）和创伤后应激症状（PTSS）是机动车碰撞的常见后遗症，与单独的结果相比，与更大的残疾相关，并且在女性中比男性更普遍。在目前的研究中，我们评估了来自X染色体的基因转录物有助于机动车碰撞后CMSP和PTSS易感性的性别差异的证据。巢式样本来自一项对非裔美国人的纵向研究，并在机动车碰撞后6个月评估CMSP（0-10数字评定量表）和PTSS（事件影响量表，修订版）结局。对血液RNA进行测序（n= 101），并使用逻辑回归分析评价X染色体mRNA表达水平与共病CMSP和PTSS结局之间的关系。在女性中，预测CMSP和PTSS的创伤周围X染色体mRNA的不成比例数量是先前发现的逃避X染色体失活的基因（11/40，z=-2.9，p = .004）。评估这些基因之间的基因本体关系的二级分析确定了已知影响神经元可塑性的基因的富集。此外，X染色体失活的两个关键调节因子X失活特异性转录本（XIST）和阴阳1号（YY 1）的表达关系在发生CMSP和PTSS的女性中不同。总之，这些数据表明，逃避失活的X染色体基因可能有助于机动车碰撞后对CMSP和PTSS易感性的性别差异。
Co‐morbid chronic musculoskeletal pain (CMSP) and posttraumatic stress symptoms (PTSS) are frequent sequelae of motor vehicle collision, are associated with greater disability than either outcome alone, and are more prevalent in women than men. In the current study we assessed for evidence that gene transcripts originating from the X chromosome contribute to sex differences in vulnerability to CMSP and PTSS after motor vehicle collision. Nested samples were drawn from a longitudinal study of African American individuals, and CMSP (0–10 numeric rating scale) and PTSS (impact of events scale, revised) outcomes were assessed 6 months following motor vehicle collision. Blood RNA were sequenced (n= 101) and the relationship between X chromosome mRNA expression levels and co‐morbid CMSP and PTSS outcomes was evaluated using logistic regression analyses. A disproportionate number of peritraumatic X chromosome mRNA predicting CMSP and PTSS in women were genes previously found to escape X chromosome inactivation (11/40,z= −2.9,p= .004). Secondary analyses assessing gene ontology relationships between these genes identified an enrichment in genes known to influence neuronal plasticity. Further, the relationship of expression of two critical regulators of X chromosome inactivation, X‐inactive specific transcript (XIST)and Yin Yang 1(YY1), was different in women developing CMSP and PTSS. Together, these data suggest that X chromosome genes that escape inactivation may contribute to sex differences in vulnerability to CMSP and PTSS after motor vehicle collision.